In:
Anesthesiology, Ovid Technologies (Wolters Kluwer Health), Vol. 132, No. 6 ( 2020-06-01), p. 1469-1481
Abstract:
Sevoflurane is commonly used for cervical cancer surgery, but its effect on cervical cancer cell biology remains unclear. This mechanistic study explores how sevoflurane affects the proliferation and metastatic potential of immortalized cervical cancer cell lines. Methods Cultured cervical cancer Caski and HeLa lines were exposed to 1, 2, or 3% sevoflurane for 2 or 4 h. Cell proliferation was determined through the Kit-8 assay and Ki-67 immunofluorescent staining. Cell migration and invasion were evaluated with the Transwell assay. Immunofluorescent staining and Western blot analysis were used to identify sevoflurane-induced morphological and biochemical changes. Results Sevoflurane exposure for either 2 or 4 h significantly increased HeLa cell proliferation in a time- and concentration-dependent manner to be 106 ± 2.7% and 107 ± 1.4% relative to the controls (n = 10; P = 0.036; P = 0.022) at 24 h after exposure and to be 106 ± 2.2% and 106 ± 1.7% relative to the controls (n = 10; P = 0.031; P = 0.023) at the highest concentration of 3% sevoflurane studied, respectively, but not Caski cells. Sevoflurane promoted invasion ability (1.63 ± 0.14 and 1.92 ± 0.12 relative to the controls) and increased cell size (1.69 ± 0.21 and 1.76 ± 0.13 relative to the controls) of Caski and HeLa cells (n = 6; all P & lt; 0.001), respectively. Sevoflurane increased histone deacetylase 6 expression in both cells, and histone deacetylase 6 knockdown abolished the prometastatic effects of sevoflurane. Sevoflurane also induced deacetylation of α-tubulin in a histone deacetylase 6–dependent manner. The protein kinase B (AKT) or extracellular regulated protein kinase (ERK1/2) phosphorylation inhibition attenuated sevoflurane-induced histone deacetylase 6 expression. Conclusions Sevoflurane enhanced proliferation, migration, and invasion of immortalized cervical cancer cells, which was likely associated with increasing histone deacetylase 6 expression caused by phosphatidylinositide 3-kinase/AKT- and ERK1/2-signaling pathway activation. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New
Type of Medium:
Online Resource
ISSN:
0003-3022
DOI:
10.1097/ALN.0000000000003129
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2020
detail.hit.zdb_id:
2016092-6
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